We have studied the mechanisms by which HIV-1 Tat and HTLV-I Tax proteins activate transcription. Recent finding relevant to the HIV-1 system include the following: 1) We have obtained evidence that Tat functions as a transcriptional adaptor that indirectly activates the HIV-1 LTR only in the setting of upstream "enhancers." 2) We have implicated a novel non-transcriptional function in Tat that influences HIV-1 infectivity. 3) We have determined that differences in the basic RNA-binding domains of HIV-1 Tat and HIV-2 Tat confer type specific transactivation of the respective LTRs. 4) We have defined the RNA-binding domain of a TAR-RNA- binding protein TRBP, which categorizes this protein into the family of RNA-binding proteins that includes human dsI kinase and Drosophila Staufen. For the HTLV-I system, recent accomplishments include: 1) the demonstration that HTLV-I Tax protein induces the formation of micro- nuclei in mammalian cells. 2) The characterization of an activation domain and a targetting domain in Tax. A third area of interest for the laboratory is the study of ribozymes. We have constructed five different ribozymes each targetted to an independent locus in the HIV-1 genome. We have also made transgenic mice that contain ribozyme-genes which direct synthesis of ribozymes capable of cleaving HIV-1 RNAs. Ongoing studies in the laboratory have also delineated that ribozymes can be used as thermal stable enzymes.